DESCRIPTION (Applicant's Abstract): Dietary supplements containing plant-derived ephedrine (ma huang) and caffeine (guarana) are widely promoted and used for weight loss, body building and exercise enhancement. Amidst reports of numerous adverse events, regulatory changes regarding ephedrine/caffeine-containing dietary supplements are being considered including changes in warning statements, dose limits and product claims. Few scientific studies have addressed the pharmacologic effects of plant-derived ephedrine and caffeine during rest or exercise. Drs Haller and Benowitz propose clinical research studies aimed at generating pharmacokinetic and pharmacodynamic data on ma huang/guarana-containing supplements to guide regulatory policy regarding the safety of marketing these products. Specific studies will examine the following: Hypothesis 1. These products are not subject to the same pre-market testing requirements as drugs and may contain more or less quantities of active constituents than declared on the product label. We aim to meausre levels of ephedrine alkaloids and methylxanthines in 4 lots of 6 commercial brands and perform a broad screen for drugs and contaminants. Hypothesis 2: Plant-derived ephedrine and caffeine may have different pharmacological properties than pure rug onus. Other herbal ingredients in commercial products may augment the stimulant effects of ephedrine and caffeine. We aim to characterize the pharmacokinetics of plant-derived ephedrine and caffeine taken in combination with other herbs as marketed compared to pure ephedrine and caffeine, alone and in combination, and measure clinical effects under resting conditions. Hypothesis 3: Increases in heart rate and blood pressure that occur during exercise may be augmented by sympathomirruetic effects of ephedrine and caffeine taken together. Other herbal ingredients in thermogenic supplements may aggravate these stimulant effects. We aim to compare the clinical effects of plant-derived ephedrine and caffeine dietary supplements compared to pure ephedrine and caffeine alone and together when taken prior to strenuous exercise. Additional studies will address the effects of individual risk factors such as gender, hypertension and diabetes and dose response and multiple dose regimens. The long-term objective for the proposed studies is to develop Dr. Haller into an independent career clinical researcher in this field of study.